RESUMEN
BACKGROUND: Loop diuretics are a primary therapy for the symptomatic treatment of heart failure (HF), but whether torsemide improves patient symptoms and quality of life better than furosemide remains unknown. As prespecified secondary end points, the TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) compared the effect of torsemide versus furosemide on patient-reported outcomes among patients with HF. METHODS: TRANSFORM-HF was an open-label, pragmatic, randomized trial of 2859 patients hospitalized for HF (regardless of ejection fraction) across 60 hospitals in the United States. Patients were randomly assigned in a 1:1 ratio to a loop diuretic strategy of torsemide or furosemide with investigator-selected dosage. This report examined effects on prespecified secondary end points, which included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; assessed as adjusted mean difference in change from baseline; range, 0-100 with 100 indicating best health status; clinically important difference, ≥5 points) and Patient Health Questionnaire-2 (range, 0-6; score ≥3 supporting evaluation for depression) over 12 months. RESULTS: Baseline data were available for 2787 (97.5%) patients for KCCQ-CSS and 2624 (91.8%) patients for Patient Health Questionnaire-2. Median (interquartile range) baseline KCCQ-CSS was 42 (27-60) in the torsemide group and 40 (24-59) in the furosemide group. At 12 months, there was no significant difference between torsemide and furosemide in change from baseline in KCCQ-CSS (adjusted mean difference, 0.06 [95% CI, -2.26 to 2.37]; P=0.96) or the proportion of patients with Patient Health Questionnaire-2 score ≥3 (15.1% versus 13.2%: P=0.34). Results for KCCQ-CSS were similar at 1 month (adjusted mean difference, 1.36 [95% CI, -0.64 to 3.36]; P=0.18) and 6-month follow-up (adjusted mean difference, -0.37 [95% CI, -2.52 to 1.78]; P=0.73), and across subgroups by ejection fraction phenotype, New York Heart Association class at randomization, and loop diuretic agent before hospitalization. Irrespective of baseline KCCQ-CSS tertile, there was no significant difference between torsemide and furosemide on change in KCCQ-CSS, all-cause mortality, or all-cause hospitalization. CONCLUSIONS: Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 months. The effects of torsemide and furosemide on patient-reported outcomes were similar regardless of ejection fraction, previous loop diuretic use, and baseline health status. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03296813.
Asunto(s)
Furosemida , Insuficiencia Cardíaca , Humanos , Furosemida/uso terapéutico , Torasemida/uso terapéutico , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/efectos adversos , Calidad de Vida , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Volumen SistólicoRESUMEN
BACKGROUND: The STRONG-HF trial showed that high-intensity care (HIC) consisting of rapid up-titration of guideline-directed medical therapy (GDMT) and close follow-up reduced all-cause death or heart failure (HF) readmission at 180 days compared to usual care (UC). We hypothesized that significant differences in patient characteristics, management, and outcomes over the enrolment period may exist. METHODS: Two groups of the 1,078 patients enrolled in STRONG-HF were created according to the order of enrolment within center. The early group consisted of the first 10 patients enrolled at each center (N = 342) and the late group consisted of the following patients (N = 736). RESULTS: Late enrollees were younger, had more frequently reduced ejection fraction, slightly lower NT-proBNP and creatinine levels compared with early enrollees. The primary outcome occurred less frequently in early compared to late enrollees (15% vs. 21%, aHR 0.65, 95% CI 0.42-0.99, P = .044). No treatment-by-enrolment interaction was seen in respect to the average percentage of optimal dose of GDMT after randomization, which was consistently higher in early and late patients randomized to HIC compared to UC. The higher use of renin-angiotensin-inhibitors in the HIC arm was more pronounced in the late enrollees both after randomization (interaction-P = .013) and at 90 days (interaction-P < .001). No interaction was observed for safety events. Patients randomized late to UC displayed a trend toward more severe outcomes (26% vs. 16%, P = .10), but the efficacy of HIC showed no interaction with the enrolment group (aHR 0.77, 95% CI 0.35-1.67 in early and 0.58, 95% CI 0.40-0.83 in late enrollees, adjusted interaction-P = .51) with similar outcomes in the HIC arm in late and early enrollees (16% vs. 13%, P = .73). CONCLUSIONS: Late enrollees have different clinical characteristics and higher event rates compared to early enrollees. GDMT implementation in the HIC arm robustly achieved similar doses with consistent efficacy in early and late enrollees, mitigating the higher risk of adverse outcome in late enrollees. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03412201.
Asunto(s)
Insuficiencia Cardíaca , Volumen Sistólico , Humanos , Masculino , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/terapia , Anciano , Persona de Mediana Edad , Volumen Sistólico/fisiología , Péptido Natriurético Encefálico/sangre , Resultado del Tratamiento , Factores de Tiempo , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Fragmentos de Péptidos/sangre , Causas de Muerte/tendencias , Readmisión del Paciente/estadística & datos numéricos , Antagonistas de Receptores de Angiotensina/uso terapéuticoRESUMEN
BACKGROUND: The use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in Veterans Affairs (VA) patients hospitalized with heart failure (HF) has not been reported previously. METHODS: VA electronic health record data were used to identify patients hospitalized for HF (primary or secondary diagnosis) from 01/2019-11/2022. Patients with SGLT2i allergy, advanced/end-stage chronic kidney disease (CKD) or advanced HF therapies were excluded. We identified factors associated with discharge SGLT2i prescriptions for patients hospitalized due to HF in 2022. We also compared SGLT2i and angiotensin receptor-neprilysin inhibitor (ARNI) prescription rates. Hospital-level variations in SGLT2i prescriptions were assessed via the median odds ratio. RESULTS: A total of 69,680 patients were hospitalized due to HF; 10.3% were prescribed SGLT2i at discharge (4.4% newly prescribed, 5.9% continued preadmission therapy). SGLT2i prescription increased over time and was higher in patients with HFrEF and primary HF. Among 15,762 patients hospitalized in 2022, SGLT2i prescription was more likely in patients with diabetes (adjusted odds ratio [aOR] 2.27; 95% confidence interval [CI]: 2.09-2.47) and ischemic heart disease (aOR 1.14; 95% CI: 1.03-1.26). Patients with increased age (aOR 0.77 per 10 years; 95% CI: 0.73-0.80) and lower systolic blood pressure (aOR 0.94 per 10 mmHg; 95% CI: 0.92-0.96) were less likely to be prescribed SGLT2i, and SGLT2i prescription was not more likely in patients with CKD (aOR 1.07; 95% CI 0.98-1.16). The adjusted median odds ratio suggested a 1.8-fold variation in the likelihood that similar patients at 2 random VA sites were prescribed SGLT2i (range 0-21.0%). In patients with EF ≤ 40%, 30.9% were prescribed SGLT2i while 26.9% were prescribed ARNI (P < 0.01). CONCLUSION: One-tenth of VA patients hospitalized for HF were prescribed SGLT2i at discharge. Opportunities exist to reduce variation in SGLT2i prescription rates across hospitals and to promote its use in patients with CKD and older age.
RESUMEN
BACKGROUND: Differences in demographics, risk factors, and clinical characteristics may contribute to variations in men and women in terms of the prevalence, clinical setting, and outcomes associated with worsening heart failure (WHF) events. We sought to describe sex-based differences in the epidemiology, clinical characteristics, and outcomes associated with WHF events across clinical settings. METHODS AND RESULTS: We examined adults diagnosed with HF from 2010 to 2019 within a large, integrated health care delivery system. Electronic health record data were accessed for hospitalizations, emergency department (ED) visits and observation stays, and outpatient encounters. WHF was identified using validated natural language processing algorithms and defined as ≥1 symptom, ≥2 objective findings (including ≥1 sign), and ≥1 change in HF-related therapy. Incidence rates and associated outcomes for WHF were compared across care setting by sex. We identified 1,122,368 unique clinical encounters with a diagnosis code for HF, with 124,479 meeting WHF criteria. These WHF encounters existed among 102,116 patients, of whom 48,543 (47.5%) were women and 53,573 (52.5%) were men. Women experiencing WHF were older and more likely to have HF with preserved ejection fraction compared with men. The clinical settings of WHF were similar among women and men: hospitalizations (36.8% vs 37.7%), ED visits or observation stays (11.8% vs 13.4%), and outpatient encounters (4.4% vs 4.9%). Women had lower odds of 30-day mortality after an index hospitalization (adjusted odds ratio 0.88, 95% confidence interval 0.83-0.93) or ED visit or observation stay (adjusted odds ratio 0.86, 95% confidence interval 0.75-0.98) for WHF. CONCLUSIONS: Women and men contribute similarly to WHF events across diverse clinical settings despite marked differences in age and left ventricular ejection fraction.
Asunto(s)
Insuficiencia Cardíaca , Aprendizaje del Sistema de Salud , Humanos , Femenino , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Masculino , Anciano , Persona de Mediana Edad , Factores Sexuales , Progresión de la Enfermedad , Estudios Retrospectivos , Hospitalización/estadística & datos numéricos , Factores de Riesgo , Anciano de 80 o más Años , Incidencia , Servicio de Urgencia en Hospital , Volumen Sistólico/fisiologíaRESUMEN
BACKGROUND: The approved use of transcatheter aortic valve replacement (TAVR) for aortic stenosis has expanded substantially over time. However, gaps remain with respect to accurately delineating risk for poor clinical and patient-centered outcomes. Our objective was to develop prediction models for 30-day clinical and patient-centered outcomes after TAVR within a large, diverse community-based population. METHODS: We identified all adults who underwent TAVR between 2013-2019 at Kaiser Permanente Northern California, an integrated healthcare delivery system, and were monitored for the following 30-day outcomes: all-cause death, improvement in quality of life, all-cause hospitalizations, all-cause emergency department (ED) visits, heart failure (HF)-related hospitalizations, and HF-related ED visits. We developed prediction models using gradient boosting machines using linked demographic, clinical and other data from the Society for Thoracic Surgeons (STS)/American College of Cardiology (ACC) TVT Registry and electronic health records. We evaluated model performance using area under the curve (AUC) for model discrimination and associated calibration plots. We also evaluated the association of individual predictors with outcomes using logistic regression for quality of life and Cox proportional hazards regression for all other outcomes. RESULTS: We identified 1,565 eligible patients who received TAVR. The risks of adverse 30-day post-TAVR outcomes ranged from 1.3% (HF hospitalizations) to 15.3% (all-cause ED visits). In models with the highest discrimination, discrimination was only moderate for death (AUC 0.60) and quality of life (AUC 0.62), but better for HF-related ED visits (AUC 0.76). Calibration also varied for different outcomes. Importantly, STS risk score only independently predicted death and all-cause hospitalization but no other outcomes. Older age also only independently predicted HF-related ED visits, and race/ethnicity was not significantly associated with any outcomes. CONCLUSIONS: Despite using a combination of detailed STS/ACC TVT Registry and electronic health record data, predicting short-term clinical and patient-centered outcomes after TAVR remains challenging. More work is needed to identify more accurate predictors for post-TAVR outcomes to support personalized clinical decision making and monitoring strategies.
Asunto(s)
Estenosis de la Válvula Aórtica , Insuficiencia Cardíaca , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Estados Unidos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Calidad de Vida , Resultado del Tratamiento , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/epidemiología , Factores de Riesgo , Insuficiencia Cardíaca/etiología , Sistema de Registros , Válvula Aórtica/cirugíaRESUMEN
BACKGROUND: Contemporary outcomes for aortic stenosis (AS) and the association between physician-assessed AS severity and quantitative parameters is poorly understood. We aimed to evaluate AS natural history, compare outcomes for physicians' AS assessment vs. quantitative parameters, and identify AS parameters with the most explanatory power. METHODS: We ascertained physician-assessed AS severity, echocardiographic parameters, and clinical data for 546,769 patients from 2008-2018, examined multivariable associations of physician-assessed AS severity and number of quantitative severe AS parameters with death, cardiovascular hospitalization, and aortic valve replacement, and estimated the relative contribution of different quantitative AS parameters on outcomes. RESULTS: Among 49,604 AS patients (mean [SD] age 77 [11] years), 17.6% had moderate, 3.6% moderate-severe, and 9.4% severe AS. During median 3.7 [IQR 1.7-6.8] years, physician-assessed AS severity strongly correlated with outcomes, with moderate AS patients tracking closest to mild AS, and moderate-to-severe AS patients more comparable to severe AS. Although the number of quantitative severe AS parameters strongly predicted outcomes (adjusted HR [95% CI] for death 1.40 [1.34-1.46], 1.70 [1.56-1.85], and 1.78 [1.63-1.94] for 1, 2, and 3 parameters, respectively), aortic valve area <1.0 cm2 was the most frequent severe AS parameter, explained the largest relative contribution (67%), and was common in patients classified as moderate (21%) or moderate-severe (56%) AS. CONCLUSIONS: Physician-assessed AS severity predicts outcomes, with cumulative effects for each severe AS parameter. Moderate AS includes a wide spectrum of patients, with discordant AVA <1.0 cm2 being both common and predictive. Better identification of non-classical severe AS phenotypes may improve outcomes.
Asunto(s)
Estenosis de la Válvula Aórtica , Humanos , Anciano , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Ecocardiografía , Catéteres , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The clinical usefulness of remote telemonitoring to reduce postdischarge health care use and death in adults with heart failure (HF) remains controversial. METHODS AND RESULTS: Within a large integrated health care delivery system, we matched patients enrolled in a postdischarge telemonitoring intervention from 2015 to 2019 to patients not receiving telemonitoring at up to a 1:4 ratio on age, sex, and calipers of a propensity score. Primary outcomes were readmissions for worsening HF and all-cause death within 30, 90, and 365 days of the index discharge; secondary outcomes were all-cause readmissions and any outpatient diuretic dose adjustments. We matched 726 patients receiving telemonitoring to 1985 controls not receiving telemonitoring, with a mean age of 75 ± 11 years and 45% female. Patients receiving telemonitoring did not have a significant reduction in worsening HF hospitalizations (adjusted rate ratio [aRR] 0.95, 95% confidence interval [CI] 0.68-1.33), all-cause death (adjusted hazard ratio 0.60, 95% CI 0.33-1.08), or all-cause hospitalization (aRR 0.82, 95% CI 0.65-1.05) at 30 days, but did have an increase in outpatient diuretic dose adjustments (aRR 1.84, 95% CI 1.44-2.36). All associations were similar at 90 and 365 days postdischarge. CONCLUSIONS: A postdischarge HF telemonitoring intervention was associated with more diuretic dose adjustments but was not significantly associated with HF-related morbidity and mortality.
Asunto(s)
Insuficiencia Cardíaca , Telemedicina , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Cuidados Posteriores , Alta del Paciente , Insuficiencia Cardíaca/terapia , Hospitalización , Aceptación de la Atención de Salud , DiuréticosRESUMEN
Iron deficiency is present in approximately 50% of patients with symptomatic heart failure and is independently associated with worse functional capacity, lower quality of, life and increased mortality. The purpose of this document is to summarize current knowledge of how iron deficiency is defined in heart failure and its epidemiology and pathophysiology, as well as pharmacological considerations for repletion strategies. This document also summarizes the rapidly expanding array of clinical trial evidence informing when, how, and in whom to consider iron repletion.
Asunto(s)
Anemia Ferropénica , Insuficiencia Cardíaca , Deficiencias de Hierro , Humanos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/complicaciones , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/epidemiología , HierroRESUMEN
BACKGROUND: Acute decompensated heart failure accounts for more than 1 million hospitalizations in the United States annually. Whether the initiation of sacubitril-valsartan therapy is safe and effective among patients who are hospitalized for acute decompensated heart failure is unknown. METHODS: We enrolled patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States. After hemodynamic stabilization, patients were randomly assigned to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or enalapril (target dose, 10 mg twice daily). The primary efficacy outcome was the time-averaged proportional change in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration from baseline through weeks 4 and 8. Key safety outcomes were the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema. RESULTS: Of the 881 patients who underwent randomization, 440 were assigned to receive sacubitril-valsartan and 441 to receive enalapril. The time-averaged reduction in the NT-proBNP concentration was significantly greater in the sacubitril-valsartan group than in the enalapril group; the ratio of the geometric mean of values obtained at weeks 4 and 8 to the baseline value was 0.53 in the sacubitril-valsartan group as compared with 0.75 in the enalapril group (percent change, -46.7% vs. -25.3%; ratio of change with sacubitril-valsartan vs. enalapril, 0.71; 95% confidence interval [CI], 0.63 to 0.81; P<0.001). The greater reduction in the NT-proBNP concentration with sacubitril-valsartan than with enalapril was evident as early as week 1 (ratio of change, 0.76; 95% CI, 0.69 to 0.85). The rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups. CONCLUSIONS: Among patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure, the initiation of sacubitril-valsartan therapy led to a greater reduction in the NT-proBNP concentration than enalapril therapy. Rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups. (Funded by Novartis; PIONEER-HF ClinicalTrials.gov number, NCT02554890 .).
Asunto(s)
Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Neprilisina/antagonistas & inhibidores , Tetrazoles/uso terapéutico , Valsartán/uso terapéutico , Enfermedad Aguda , Anciano , Compuestos de Bifenilo , Gasto Cardíaco Bajo , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Combinación de Medicamentos , Enalapril/uso terapéutico , Femenino , Insuficiencia Cardíaca/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Volumen SistólicoRESUMEN
BACKGROUND: Adults with chronic kidney disease (CKD) are at increased risk of heart failure (HF) morbidity and mortality. Despite well-characterized abnormalities in cardiac structure in CKD, it remains unclear how to optimally leverage echocardiography to risk stratify CKD patients. METHODS: We evaluated associations between echocardiographic parameters and risk of HF hospitalization and death using Cox proportional hazard models and forward selection with integrated discrimination improvement (IDI). RESULTS: The study included 3,505 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Mean age was 59 ± 11 years, HF prevalence was 10%, and mean left ventricular (LV) ejection fraction (LVEF) was 54 ± 9%. During median 11 (interquartile range: 8-12) years of follow-up, event rates per 100-person years for HF hospitalizations and death, respectively, were 9.4 (95% Confidence Interval [CI]: 7.9-11.3) and 8.9 (95% CI: 7.6-10.5) for participants with LVEF <40%, 3.5 (95% CI: 3.0-4.2) and 4.6 (95% CI: 4.0-5.2) for patients with LVEF 40% to 49%, and 1.9 (95% CI: 1.7-2.1) and 3.1 (95% CI: 2.9-3.3) for patients with LVEF >50%. The rate of HF hospitalizations and deaths increased with lower eGFR across all LVEF categories. LV mass index, LVEF, and LV geometry had the strongest association with outcomes but provided modest incremental prognostic value to a baseline clinical model (IDI = 0.14 and ΔAUC = 0.017 for HF hospitalization, IDI = 0.12 and ΔAUC = 0.008 for death). CONCLUSIONS: Baseline echocardiographic parameters are independently associated with increased risk of subsequent HF morbidity and mortality but provide only marginal incremental prognostic utility beyond clinical characteristics in the setting of CKD.
Asunto(s)
Insuficiencia Cardíaca , Insuficiencia Renal Crónica , Adulto , Anciano , Ecocardiografía , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
AIM: To determine the trends in hospitalizations for heart failure (HF), acute myocardial infarction (AMI), and stroke in the United States (US). METHOD AND RESULTS: A retrospective analysis of the National Inpatient Sample weighted data between January 1, 2004 and December 31, 2018 which included hospitalized adults ≥18 years with a primary discharge diagnosis of HF, AMI, or stroke using International Classification of Diseases-9/10 administrative codes. Main outcomes were hospitalization for HF, AMI, and stroke per 1000 United States adults, length of stay, and in-hospital mortality. There were 33.4 million hospitalizations for HF, AMI, and stroke, with most being for HF (48%). After the initial decline in HF hospitalizations (5.3 hospitalizations/1000 US adults in 2004 to 4 hospitalizations/1000 US adults in 2013, P < .001), there was a progressive increase in HF hospitalizations between 2013 and 2018 (4.0 hospitalizations/1000 US adults in 2013 to 4.9 hospitalizations/1000 US adults in 2018; P < .001). Hospitalization for AMI decreased (3.1 hospitalizations/1000 US adults in 2004 to 2.5 hospitalizations/1000 US adults in 2010, P < .001) and remained stable between 2010 and 2018. There was no significant change for hospitalization for stroke between 2004 and 2011 (2.3 hospitalizations/1000 US adults in 2004 vs 2.3 hospitalizations per 1000 US adults in 2011, P = .614); however, there was a small but significant increase in hospitalization for stroke after 2011 that reached 2.5 hospitalizations/1000 US adults in 2018. Adjusted length of stay and in-hospital mortality decreased for HF, AMI, and stroke hospitalizations. CONCLUSIONS: In contrast to the trend of AMI and stroke hospitalizations, a progressive increase in hospitalizations for HF has occurred since 2013. From 2004 to 2018, in-hospital mortality has decreased for HF, AMI, and stroke hospitalizations.
Asunto(s)
Insuficiencia Cardíaca , Infarto del Miocardio , Accidente Cerebrovascular , Adulto , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Mortalidad Hospitalaria , Hospitalización , Humanos , Infarto del Miocardio/epidemiología , Infarto del Miocardio/terapia , Estudios Retrospectivos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Renin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection coronavirus disease 2019 (COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes. METHODS: The RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]) and the intention-to-treat principle. RESULTS: Overall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5); P = .60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 [95% CI 1.06-2.62]; P = .027); RAASi discontinuation increased brain natriuretic peptide levels (% change from baseline: +16.7% vs -27.5%; P = .024) and the incidence of acute heart failure (33% vs 4.2%, P = .016). CONCLUSION: RAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased brain natriuretic peptide levels and may increase risk of acute heart failure; where possible, RAASi should be continued.
Asunto(s)
COVID-19 , Insuficiencia Cardíaca , Adulto , Anciano , Aldosterona , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/uso terapéutico , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Hospitales , Humanos , Péptido Natriurético Encefálico , Sistema Renina-AngiotensinaRESUMEN
BACKGROUND: Inability to adhere to nutritional recommendations is common and linked to worse outcomes in patients with nutrition-sensitive conditions. OBJECTIVES: The purpose of this study is to evaluate whether medically tailored meals (MTMs) improve outcomes in recently discharged adults with nutrition-sensitive conditions compared with usual care. RESEARCH DESIGN: Remote pragmatic randomized trial. SUBJECTS: Adults with heart failure, diabetes, or chronic kidney disease being discharged home between April 27, 2020, and June 9, 2021, from 5 hospitals within an integrated health care delivery system. MEASURES: Participants were prerandomized to 10 weeks of MTMs (with or without virtual nutritional counseling) compared with usual care. The primary outcome was all-cause hospitalization within 90 days after discharge. Exploratory outcomes included all-cause and cause-specific health care utilization and all-cause death within 90 days after discharge. RESULTS: A total of 1977 participants (MTMs: n=993, with 497 assigned to also receive virtual nutritional counseling; usual care: n=984) were enrolled. Compared with usual care, MTMs did not reduce all-cause hospitalization at 90 days after discharge [adjusted hazard ratio, aHR: 1.02, 95% confidence interval (CI), 0.86-1.21]. In exploratory analyses, MTMs were associated with lower mortality (aHR: 0.65, 95% CI, 0.43-0.98) and fewer hospitalizations for heart failure (aHR: 0.53, 95% CI, 0.33-0.88), but not for any emergency department visits (aHR: 0.95, 95% CI, 0.78-1.15) or diabetes-related hospitalizations (aHR: 0.75, 95% CI, 0.31-1.82). No additional benefit was observed with virtual nutritional counseling. CONCLUSIONS: Provision of MTMs after discharge did not reduce risk of all-cause hospitalization in adults with nutrition-sensitive conditions. Additional large-scale randomized controlled trials are needed to definitively determine the impact of MTMs on survival and cause-specific health care utilization in at-risk individuals.
Asunto(s)
Insuficiencia Cardíaca , Hospitalización , Adulto , Servicio de Urgencia en Hospital , Insuficiencia Cardíaca/terapia , Humanos , Comidas , Alta del PacienteRESUMEN
PURPOSE OF REVIEW: COVID-19 is now a global pandemic and the illness affects multiple organ systems, including the cardiovascular system. Long-term cardiovascular consequences of COVID-19 are not yet fully characterized. This review seeks to consolidate available data on long-term cardiovascular complications of COVID-19 infection. RECENT FINDINGS: Acute cardiovascular complications of COVID-19 infection include myocarditis, pericarditis, acute coronary syndrome, heart failure, pulmonary hypertension, right ventricular dysfunction, and arrhythmia. Long-term follow-up shows increased incidence of arrhythmia, heart failure, acute coronary syndrome, right ventricular dysfunction, myocardial fibrosis, hypertension, and diabetes mellitus. There is increased mortality in COVID-19 patients after hospital discharge, and initial myocardial injury is associated with increased mortality. Emerging data demonstrates increased incidence of cardiovascular illness and structural changes in recovered COVID-19 patients. Future research will be important in understanding the clinical significance of these structural abnormalities, and to determine the effect of vaccines on preventing long-term cardiovascular complications.
Asunto(s)
Síndrome Coronario Agudo , COVID-19 , Insuficiencia Cardíaca , Disfunción Ventricular Derecha , Arritmias Cardíacas , COVID-19/complicaciones , Corazón , Humanos , SARS-CoV-2RESUMEN
OBJECTIVE: The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD). BACKGROUND: IPE is a highly purified and stable omega-3 fatty acid prescription medication that is approved for cardiovascular risk reduction in high-risk adults on statin therapy with elevated triglycerides. Preclinical data and clinical observations suggest that IPE may have pleiotropic effects including antiviral and anti-inflammatory properties that may prevent or reduce the downstream sequelae and cardiopulmonary consequences of viral URIs. METHODS: MITIGATE is a virtual, electronic health record-based, open-label, randomized, pragmatic clinical trial enrolling â¼16,500 participants within Kaiser Permanente Northern California - a fully integrated and learning health care delivery system with 21 hospitals and >255 ambulatory clinics serving â¼4.5 million members. Adults ≥50 years with established ASCVD and no prior history of coronavirus disease 2019 (COVID-19) will be prospectively identified and pre-randomized in a 1:10 allocation ratio (â¼ 1,500 IPE: â¼15,000 usual care) stratified by age and previous respiratory health status to the intervention (IPE 2 grams by mouth twice daily with meals) vs the control group (usual care) for a minimum follow-up duration of 6 months. The co-primary endpoints are moderate-to-severe laboratory-confirmed viral URI and worst clinical status due to a viral URI at any point in time. CONCLUSION: The MITIGATE study will inform clinical practice by providing evidence on the real-world clinical effectiveness of pretreatment with IPE to prevent and/or reduce the sequelae of laboratory-confirmed viral URIs in a high-risk cohort of patients with established ASCVD.
Asunto(s)
Aterosclerosis/complicaciones , COVID-19/complicaciones , Enfermedades Cardiovasculares/prevención & control , Ácido Eicosapentaenoico/análogos & derivados , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anciano , Enfermedades Cardiovasculares/complicaciones , Ácido Eicosapentaenoico/uso terapéutico , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/virologíaRESUMEN
PURPOSE OF THE REVIEW: In the decades following the advent of percutaneous coronary intervention, the optimal treatment strategy for managing stable ischemic heart disease has remained a topic of debate. The purpose of this review is to discuss current literature that provides insight into preferred treatment strategies for managing stable coronary artery disease. RECENT FINDINGS: The COURAGE trial (2007) compared patients with stable coronary artery disease treated with percutaneous coronary intervention plus optimal medical therapy versus optimal medical therapy alone and found no difference in death from any cause and non-fatal myocardial infarction at 4.6 years. The more recent ISCHEMIA trial (2020) compared an initial invasive revascularization strategy with optimal medical therapy to optimal medical therapy alone and similarly found no difference in death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest at 5 years. When applied to a broad population with stable coronary artery disease, evidence suggests there is no benefit to an initial invasive revascularization strategy relative to optimal medical therapy alone. Further investigation is warranted to determine whether there are subgroups of individuals that may benefit from earlier revascularization.
Asunto(s)
Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Isquemia Miocárdica , Intervención Coronaria Percutánea , Enfermedad de la Arteria Coronaria/terapia , Humanos , Isquemia Miocárdica/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: Prediction of readmission and death after hospitalization for heart failure (HF) is an unmet need. AIM: We evaluated the ability of clinical parameters, NT-proBNP level and noninvasive lung impedance (LI), to predict time to readmission (TTR) and time to death (TTD). METHODS AND RESULTS: The present study is a post hoc analysis of the IMPEDANCE-HF extended trial comprising 290 patients with LVEF ≤45% and New York Heart Association functional class II-IV, randomized 1:1 to LI-guided or conventional therapy. Of all patients, 206 were admitted 766 times for HF during a follow-up of 57 ± 39 months. The normal LI (NLI), representing the "dry" lung status, was calculated for each patient at study entry. The current degree of pulmonary congestion (PC) compared with its dry status was represented by ΔLIR = ([measured LI/NLI] - 1) × 100%. Twenty-six parameters recorded during HF admission were used to predict TTR and TTD. To determine the parameter which mainly impacted TTR and TTD, variables were standardized, and effect size (ES) was calculated. Multivariate analysis by the Andersen-Gill model demonstrated that ΔLIRadmission (ES = 0.72), ΔLIRdischarge (ES = -3.14), group assignment (ES = 0.2), maximal troponin during HF admission (ES = 0.19), LVEF related to admission (ES = -0.22) and arterial hypertension (ES = 0.12) are independent predictors of TTR (p < 0.01, χ2 = 1,206). Analysis of ES showed that residual PC assessed by ∆LIRdischarge was the most prominent predictor of TTR. One percent improvement in predischarge PC, assessed by ∆LIRdischarge, was associated with a likelihood of TTR increase by 14% (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.13-1.15, p < 0.01) and TTD increase by 8% (HR 1.08, 95% CI 1.07-1.09, p < 0.01). CONCLUSION: The degree of predischarge PC assessed by ∆LIR is the most dominant predictor of TTR and TTD.
Asunto(s)
Insuficiencia Cardíaca , Readmisión del Paciente , Estudios de Seguimiento , Hospitalización , Humanos , Pulmón , Péptido Natriurético Encefálico , Fragmentos de Péptidos , PronósticoRESUMEN
INTRODUCTION: Acute kidney injury is a common complication of percutaneous coronary intervention and has been associated with an increased risk of death and progressive chronic kidney disease. However, whether the timing of acute kidney injury after urgent percutaneous coronary intervention could be used to improve patient risk stratification is not known. METHODS: We conducted a retrospective cohort study in adults surviving an urgent percutaneous coronary intervention between 2008 and 2013 within Kaiser Permanente Northern California, a large integrated healthcare delivery system, to evaluate the impact of acute kidney injury during hospitalization at 12 (±6), 24 (±6) and 48 (±6) hours after urgent percutaneous coronary intervention and subsequent risks of adverse outcomes within the first year after discharge. We used multivariable Cox proportional hazards models with adjustment for a high-dimensional propensity score for developing acute kidney injury after percutaneous coronary intervention to examine the associations between acute kidney injury timing and all-cause death and worsening chronic kidney disease. RESULTS: Among 7250 eligible adults undergoing urgent percutaneous coronary intervention, 306 (4.2%) had acute kidney injury at one or more of the examined time periods after percutaneous coronary intervention. After adjustment, acute kidney injury at 12 (±6) hours was independently associated with higher risks of death (adjusted hazard ratio [aHR] 3.55, 95% confidence interval [CI] 2.19-5.75) and worsening kidney function (aHR 2.40, 95% CI:1.24-4.63). Similar results were observed for acute kidney injury at 24 (±6) hours and death (aHR 3.90, 95% CI:2.29-6.66) and worsening chronic kidney disease (aHR 4.77, 95% CI:2.46-9.23). Acute kidney injury at 48 (±6) hours was associated with excess mortality (aHR 1.97, 95% CI:1.19-3.26) but was not significantly associated with worsening kidney function (aHR 0.91, 95% CI:0.42-1.98). CONCLUSIONS: Timing of acute kidney injury after urgent percutaneous coronary intervention may be differentially associated with subsequent risk of worsening kidney function but not death.
Asunto(s)
Lesión Renal Aguda/etiología , Intervención Coronaria Percutánea/efectos adversos , Lesión Renal Aguda/mortalidad , Anciano , Causas de Muerte , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Cardiorespiratory fitness (CRF) is closely linked to health status and clinical outcomes in heart failure (HF) patients. We aimed to test whether biomarkers can reflect CRF and its change over time. METHODS: This post hoc analysis used data from ambulatory cohorts of heart failure with reduced ejection fraction (HFrEF) (IRONOUT) and heart failure with preserved ejection fraction (HFpEF) (RELAX). Cardiopulmonary exercise testing, 6-minute walk distance (6MWD), and serum biomarkers were measured at baseline and 16- or 24-week follow-up (for IRONOUT and RELAX respectively). Biomarkers included N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2, growth differentiation factor-15, and Galectin-3. RESULTS: Analysis included 225 patients with HFrEF and 216 with HFpEF. Baseline peak VO2, VE/VCO2 slope, and 6MWD showed a mild correlation with the doubling of all 4 tested biomarkers in HFrEF and HFpEF. Following multivariable adjustment (including all biomarkers), the only significant association between change in biomarker and functional parameter in HFrEF was change in NT-proBNP and change in VE/VCO2 slope (3.596% increase per doubling, 95% CI 0.779-6.492, Pâ¯=â¯.012). In HFpEF, a decrease in peak VO2 was associated with an increase in NT-proBNP (-0.726â¯mL/min/kg per doubling, 95% CI -1.100 to -0.353, Pâ¯<â¯.001), and a decrease in 6MWD was associated with an increase in growth differentiation factor-15 (-31.606â¯m per doubling, 95% CI -61.404 to -1.809, Pâ¯=â¯.038). CONCLUSIONS: In these ambulatory trial cohorts, NT-proBNP was associated with baseline and change in CRF in HFrEF and HFpEF. In contrast, novel biomarkers do not appear suitable as a reliable surrogate for serial assessment of exercise capacity in HF patients given lack of consistent independent association with CRF beyond traditional risk factors and NT-proBNP.
Asunto(s)
Capacidad Cardiovascular , Galectina 3/sangre , Factor 15 de Diferenciación de Crecimiento/sangre , Insuficiencia Cardíaca/sangre , Proteína 1 Similar al Receptor de Interleucina-1/sangre , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Anciano , Biomarcadores/sangre , Proteínas Sanguíneas , Enfermedad Crónica , Femenino , Galectinas , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Volumen Sistólico/fisiología , Factores de Tiempo , Prueba de PasoRESUMEN
With few notable exceptions, drug development for heart failure (HF) has become progressively more challenging, and there remain no definitively proven therapies for patients with acute HF or HF with preserved ejection fraction. Inspection of temporal trends suggests an increasing rate of disagreement between early-phase and phase III trial end points. Preliminary results from phase II HF trials are frequently promising, but increasingly followed by disappointing phase III results. Given this potential disconnect, it is reasonable to carefully re-evaluate the purpose, design, and execution of phase II HF trials, with particular attention directed toward the surrogate end points commonly used by these studies. In this review, we offer a critical reappraisal of the role of phase II HF trials and surrogate end points, highlighting challenges in their use and interpretation, lessons learned from past experiences, and specific strengths and weaknesses of various surrogate outcomes. We conclude by proposing a series of approaches that should be considered for the goal of optimizing the efficiency of HF drug development. This review is based on discussions between scientists, clinical trialists, industry and government sponsors, and regulators that took place at the Cardiovascular Clinical Trialists Forum in Washington, DC, on December 2, 2016.